Hindler
Educating Clinical and Public
Health Laboratories About
Antimicrobial Resistance
Challenges
Janet Hindler, MCLS MT(ASCP)
UCLA Medical Center
jhindler@ucla.edu
…also working as a consultant with the
Association of Public Health Laboratories
with support from CDC
As related to clinical and public health
laboratories and antimicrobial resistance
challenges, at the conclusion of this
program, you will be able to…
to…..
♦ Describe the primary challenges for
antimicrobial susceptibility testing and
reporting (AST/R).
♦ Discuss the primary educational resources
currently available for AST/R.
♦ List measures that can be taken to enhance
knowledge about antimicrobial resistance
and improve the quality of AST results
reported.
Timeline: Some Major Antimicrobial
Resistance Events
Most of current lab workforce trained here!
1942
Penicillin-R
S. aureus
1961
MRSA
1967
1983
Penicillin-R
ESBL
S. pneumoniae
1988
1996
2002
KPC
VRSA
VRE
ESBL, extendedextended-spectrum β-lactamase (Enterobacteriaceae)
KPC, Klebsiella pneumoniae carbapenemase
MRSA, methicillinmethicillin-resistant Staphylococcus aureus
VRE, vancomycinvancomycin-resistant Enterococcus
VRSA, vancomycinvancomycin-resistant S. aureus
jhindler APUA 10/07
Hindler
What is required of USA labs
and what information is
available for AST/R?
Please note: AST/R =
antimicrobial susceptibility testing and reporting
“Specific”
Specific” mandates by accrediting / certifying
agencies for clinical and public health
laboratories regarding AST/R…
AST/R….
It is mandatory for laboratory to:
As related to AST/R…
AST/R….
Document competency of staff
Does not specifically address
AST/R
Include organisms with specific
resistance mechanisms (3 - 8/year)
Participate in proficiency testing
surveys
Perform adequate quality control
Very specific requirements for
AST/R
Perform appropriate testing /
reporting of patient specimens
Very few specific requirements for
AST/R
In terms of information for effective
AST/R, what is readily available to
clinical and public health laboratories?
Information readily available for:
Selecting organisms to test
+
Selecting drugs to test
+++
Testing methods
++++
Reporting results
++
+, little information available; ++++, much information available
available
jhindler APUA 10/07
Hindler
Sources of Information for AST/R
♦Text books / manuals
– CLSI (Clinical and Laboratory Standards
Institute) documents (primary resource)
http://www.clsi.org/
– Isenberg, HI. (ed). 2004. Clinical Microbiology
Procedures Handbook,
Handbook, 2nd edition. Sxn.
Sxn. 5.
ASM Press, Washington, DC.
– Murray, PR, EJ Baron, JH Jorgensen, ML
Landry and MA Pfaller (eds). 2007. Manual of
Clinical Microbiology,
Microbiology, 9th ed. pp. 10751075-1269.
ASM Press, Washington, DC.
Sources of Information for AST/R
(con’
(con’t)
♦Continuing education programs
sponsored by:
– Professional organizations
– Commercial companies
– Public health organizations
♦Various websites, listserves
Primary Challenges for
AST/R
jhindler APUA 10/07
Hindler
What are the primary challenges for AST/R
in clinical and public health laboratories?
♦ Performing susceptibility tests when
appropriate (limit over or under reporting)
♦ Getting access to the most recent CLSI
AST/R recommendations and keeping up with
the recommendations
♦ Applying all of the “special”
special” testing/reporting
rules (need artificial intelligence!)
What are the primary challenges for AST/R
in clinical and public health laboratories?
(con’
con’t)
♦ Dealing with conflicting recommendations
(e.g., CLSI vs. FDA breakpoints)
♦ Having confidence in performance of
commercial testing systems
♦ Deciding how far a smaller lab should go with
AST/R
♦ Defining the role of public health laboratories
♦ Communicating results effectively
Specimen: Leg wound
Diagnosis: Hypertension
GS:
Many GPC clusters
Many pleomorphic GPR
No WBCs
Should AST be
performed?
Culture:
Many coagcoag-neg staphylococcus
Many diphtheroids
Few E. colicoli-like colonies
Few ProteusProteus-like colonies
jhindler APUA 10/07
Hindler
CLSI (Clinical and Laboratory Standards
Institute, formerly NCCLS) Documents
CLSI
♦ M2M2-A9 Disk diffusion (2006)
Documents
♦ M7M7-A7 MIC (2006)
♦ *M100*M100-S17 Tables with breakpoints, QC ranges,
drugs to test (2007)
♦ M11M11-A7 Anaerobes (2007)
♦ M39M39-A2 Cumulative antibiograms (2005)
♦ 4545-A Infrequently Isolated / Fastidious Bacteria
(2006)
*updated yearly; others updated every 33-5 years
Staphylococcus aureus
AST/R Rules
Agent
Cefazolin
Clindamycin
Daptomycin
Erythromycin
Linezolid
Rule
Report “R” for MRSA even if test result is ”S”
Perform D zone test for inducible resistance if
erythromycinerythromycin-R and clindamycinclindamycin-S
Do not report on urine isolates
Only “S” breakpoint; send isolate to reference
lab if not “S”
Erythromycin results predict those for
azithromycin and clarithromycin
Do not report on urine isolates
Only “S” breakpoint; send isolate to reference
lab if not “S”
Staphylococcus aureus
AST/R Rules (con’
(con’t)
Agent
Oxacillin
Penicillin
AST/R Rules
AST/R Rules
Rule
Cefoxitin detects mecA
mecA-mediated resistance
better than oxacillin
Perform β-lactamase test if MIC ≤0.12 µg/ml
Rifampin
Add report note “rifampin should not be used
alone for antimicrobial therapy”
therapy”
Tetracycline
If S, consider doxycycline and minocycline “S”;
if R, doxycycline and/or minocycline may be “S”
Trimeth-sulfa Ignore 20% growth when determining endpoint
Trimeth--sulfa
Vancomycin
Verify any result with MIC >2 µg/ml
jhindler APUA 10/07
Hindler
How can we ensure AST/R rules and
recommendations are followed
consistently?
AST/R Rules
Need “Artificial Intelligence”
Intelligence”
♦ Flag organisms needing further testing
♦ Report appropriate drugs
♦ Edit “S” or “I” results to “R”
♦ Flag atypical / inconsistent results
AST/Report
Rules
♦ Add comments to report
Examples of FDA vs. CLSI Breakpoints
S, I, R Breakpoints (µ
(µg/ml)
Drug / bug
Oxacillin
Staphylococcus
FDA
CLSI
≤2, -, ≥4
≤2, -, ≥4
none
≤2, 4, ≥8
≤2, 4, ≥8
none
≤4, 88-16, ≥32
≤2, 44-8, ≥16
Colistin
P. aeruginosa
Tigecycline
Enterobacteriaceae
Vancomycin
S. aureus
Conflicting
recommendations
Currently, diagnostic manufacturers must use FDA breakpoints
Clinical laboratories can use CLSI or FDA breakpoints
Need “harmonization”
harmonization” of breakpoints
How well does an “I” or “R” result predict KPCs?
KPCs?
(N = 31 KPC producers; 45 nonnon-KPC producers)
Sensitivity/specificity (%)
Reliability
of methods
Carbapenem “I” or “R” result
Method
Meropenem
Imipenem
Ertapenem
Reference BMD
94/98
94/93
97/89
Etest
58/96
55/96
90/84
Disk diffusion
71/96
42/96
97/87
Vitek Legacy
52/98
55/96
NA
Vitek 2
48/96
71/96
94/93
MicroScan
84/98
74/96
100/89
Phoenix
61/98
81/96
NA
Sensititre
42/98
29/96
NA
NA, not applicable (range not low enough or drug not available on
on panel)
Anderson et al. 2007. J Clin Microbiol. 45:2723.
jhindler APUA 10/07
Hindler
Example:
types of labs
doing AST/R
= lab in 5050-75 bed rural hospital
= lab in >500 bed tertiary care center or
reference lab
What testing menu might the small rural
hospital laboratory adopt for AST/R?
♦ S. aureus
– Must all AST/R rules be considered?
♦ E. coli / Klebsiella spp.
– Should ESBL testing be performed?
– Should ertapenem be tested to detect KPC (Klebsiella
(Klebsiella
pneumoniae carbapenemase) producers?
♦ Should other bacteria be tested?
♦ Should all AST be sent out?
Smaller labs
– Turn around time considerations
and AST/R??
Issues for the small rural hospital
laboratory re: AST/R
♦ How can small lab have a limited AST/R
menu when any type of resistant
organism is possible in any patient?
♦ How can limited staff be adequately
trained to perform all AST/R reliably?
– Staff often do microbiology “part time”
time”
Smaller labs
and AST/R??
jhindler APUA 10/07
Hindler
Specimen: Peritoneal fluid
Diagnosis: Appendicitis
Pseudomonas aeruginosa
MIC (µ
(µg/ml)
ceftazidime
8S
Communicate
ciprofloxacin
1S
results effectively
gentamicin
2S
piperacillin
16 S
“Combination therapy (e.g. β-lactam + aminoglycoside
or β-lactam + fluoroquinolone) should be considered for
serious P. aeruginosa infections”
Cumulative Antibiogram
2006
Communicate
results effectively
N
Am Cfaz Cftrx Cip Gm TT-S
61
92
95
92
97
76
E. cloacae 144
-
-
71
95
88
84
221
-
-
10
76
88
-
E. coli
P. aerug
729
% Susceptible
%S data compiled according to CLSI M39M39-A2.
Public Health Labs and
AST/R
jhindler APUA 10/07
Hindler
How are public health laboratories
involved with AST/R?
♦ Most do no AST and have limited expertise in
AST
♦ If testing is done:
–
–
–
–
–
Campylobacter jejuni / coli
Neisseria gonorrhoeae
Salmonella spp.
Streptococcus pneumoniae
Staphylococcus aureus
♦ Method primarily disk diffusion and/or Etest
How are public health laboratories
involved with AST/R? (con’
(con’t)
♦ Some state PH labs are helping to educate
clinical laboratories with AST/R; examples:
– New Jersey – cumulative antibiogram project
– New York – proficiency testing program
– Washington – regional technical workshops
How are public health laboratories
involved with AST/R? (con
(con’’t)
♦ Some state PH labs have affiliation with
clinical lab (university) and can provide more
support for clinical laboratories; examples:
– Nebraska – clinical lab is resource for problem isolates
– Iowa – collect, test, provide feedback on specific isolates
♦ Some state PH labs do limited surveillance for
antimicrobial resistance
jhindler APUA 10/07
Hindler
Expectations…..
PH Lab expects Clin Lab
to provide:
Clin Lab expects PH Lab
to provide:
• Isolates w/ unusual “R” (e.g.,
VRSA)
• Verification of unusual
results (or sends to CDC)
• Technical information from
CDC / Others
• Notice of “R” events (e.g.,
VRSA)
• Notice of training events
….maybe
• Cumulative antibiogram data
…maybe
• Regional antibiogram data
• CLSI AST standards
What 10 steps can we take to educate
clinical and public health laboratories
about antimicrobial resistance challenges
and improve practices to optimize
reporting of “quality”
quality” results?
What can we do?
1. Provide the latest CLSI standards to all labs that
perform AST/R for patient care.
2. Continue to develop/promote/present educational
programs to help labs “interpret”
interpret” and apply the
latest CLSI standards (routine AST/R and cumulative
antibiograms).
3. Develop “standards of practice”
practice”
a) When to perform AST (which organisms to test from
various specimen types)
b) How to most effectively report results
c) Enhanced guidelines for interpreting results
jhindler APUA 10/07
Hindler
What else can we do?
4. Investigate ways a small rural lab could
best handle AST/R.
5. Continue to pursue harmonization of FDA
and CLSI breakpoints.
6. Encourage diagnostic manufacturers to
reevaluate their systems regularly to
determine the system’
system’s abilities to detect
resistance in “contemporary”
contemporary” pathogens.
What else can we do?
7. Encourage diagnostic manufacturers and
software vendors to improve artificial
intelligence for AST/R.
8. Develop/promote/present educational
programs to assist PH labs to better serve as
a resource (or identify an alternative
resource) for AST/R in their community.
9. Interact with accrediting and regulatory
agencies to help their surveyors identify
inappropriate AST practices that might lead
to medical errors.
What else can we do?
10. Provide validated materials (e.g., ppt.
ppt.
presentations and other) that can be used by
others to emphasize effective ways to confront
emerging resistance; audiences:
¾ Clinical lab
¾ Public health (lab/epi
(lab/epi))
¾ MDs
¾ Infection Control
¾ Pharmacy
jhindler APUA 10/07
Hindler
Counts et al. 2007. JCM. 45:2230.
Reports of recent
successes
Rosner et al. 2007. Clin Lab Sci. 20:146.
Might there be mechanisms
to further educate clinical and
public health laboratories
about antimicrobial
resistance challenges??
http://www.idsociety.org/STAARAct.htm
http://www.idsociety.org/STAARAct.htm
jhindler APUA 10/07